Lymphangiogenesis and Lymphangiogenic Growth Factors

Lymphedema is a progressive disease caused by damage to the lymphatic network. Recent development in the fields of preclinical growth factor research and lymphedema microsurgery promise new hope for lymphedema patients. In this article, we review the latest results on basic research and highlight the role of specific growth factors in normal lymphatic development and several disease states. Lymph node transfer, a new promising method in reconstructive lymphatic microsurgery, is also dependent on the lymphatic vascular regrowth and lymphangiogenic growth factors. We discuss the scientific basis of lymph node transfer and therapeutic potential of lymphangiogenic growth factors in the treatment of lymphedema.Peer reviewe

Somatosensory evoked potentials are abnormal with plagiocephaly

Publisher Copyright: © 2022 Korean Cleft Palate-Craniofacial Association.Background: Deformational plagiocephaly is usually managed conservatively, as it tends to improve over time and with the use of conser-vative measures. However, before the year 2017 we operated on patients with severe plagiocephaly and neurological symptoms at the Helsinki Cleft Palate and Craniofacial Center. Methods: Of the 20 infants with severe deformational plagiocephaly and neurological symptoms referred to us between 2014 and 2016, 10 underwent cranioplasty open reshaping of the posterior cranial vault. The parents of the last 10 patients were given information on the natural history of the condition and the patients were followed up with an outpatient protocol. The aim of this study was to gain information on the brain electrophysiology and recovery of patients after total cranial vault reconstruction by measuring the electroencephalogram (EEG) somatosensory evoked potentials (SEP; median nerve). Results: Of the 10 participants in the operation arm, six had abnormal SEP at least on the affected cerebral hemisphere and all SEPs were recorded as normal when controlled postoperatively. In the follow-up arm, eight out of 10 participants had abnormal SEP at the age of ap-proximately 24 months, and all had normalized SEPs at control visits. Conclusion: Our data suggest that cranioplasty open reshaping of the posterior cranial vault did not affect abnormal SEP-EEG recordings. We have abandoned the operations in deformational plagiocephaly patients due to findings suggesting that expanding cranioplasty is not beneficial for brain function in this patient group.Peer reviewe

Facial asymmetry in children with either unilateral lambdoid craniosynostosis or positional posterior plagiocephaly

Background In unilateral lambdoid craniosynostosis (ULC), the posteriorly situated lambdoid suture of the cranial vault fuses prematurely. Positional posterior plagiocephaly (PPP) causes flattening of the posterior side of the head, either through external forces or through underlying differences in brain development. Both conditions cause occipital flattening of the head, but the aetiology is different. Materials and Methods Eight ULC children were compared with 16 sex- and age-matched PPP children. 3D computer tomography scans of all 24 children were analysed with Dolphin imaging software. The location and symmetry of the temporomandibular joint (Co), and the symmetry of the maxillary anterior nasal spine (ANS) and the mandibular symphysis (Pgn) were analysed. Furthermore, the mandibular bone (Co-Pgn) length, corpus length, ramus height, positional changes in the external acoustic meatus (PoL) and the distance from the orbital margin to the articular fossa were measured. Results In all eight ULC children, the Co was anteriorly displaced on the affected side compared with the unaffected side. In all ULC and PPP children, the ANS, which is considered the bony maxillary midpoint, was shifted towards the affected side. In all ULC children, the mandibular bone (Co-Pgn) was shorter on the affected side. The PoL was antero-inferiorly positioned in all ULC children on the affected side compared with the unaffected side. Conclusions Our results show that both types of posterior plagiocephaly are associated with an asymmetric position of the Co and asymmetry of the mandible and maxilla. Facial asymmetry was more frequently seen in ULC than PPP children.Peer reviewe

Use of black-bone MRI in the diagnosis of the patients with posterior plagiocephaly

Ionising radiation exposure is especially harmful to brain development. The purpose of this study was to evaluate whether black-bone (BB) magnetic resonance imaging (MRI), a non-ionising imaging method, offers an alternative to ionising imaging methods such as computed tomography (CT) in the examination of cranial deformities. From 2012 to 2014, a total of 408 children were referred to the Craniofacial Centre at the Helsinki University Hospital for further examination due to flatness of the posterior skull. Fifteen of these patients required further diagnostic imaging. To avoid ionising radiation, we used an MRI protocol that included sequences for evaluation of both brain anatomy and skull bone and sutures by BB-MRI. A semi-automatic skull segmentation algorithm was developed to facilitate the visualisation. Two patients with scaphocephaly were included in the study to confirm the ability to differentiate synostosis with BB-MRI. We obtained informative 3D images using BB-MRI. Seven patients (7/15, 46.7%) had plagiocephaly on the right side and seven on the left side (7/15, 46.7%). One patient (1/15, 6.7%) had symmetric posterior flatness affecting both sides. Neither structural nor signal-intensity alterations of the brain were detected in visual analysis. BB-MRI provides an alternative to CT when imaging craniofacial deformities. BB-MRI provides not only high-quality 3D-reconstructed imaging of the bony structures and sutures but also information on brain structure in one imaging session. With further development, this method could replace ionising radiation-based methods in analysing deformities of the skull.Peer reviewe

Phase 1 Lymfactin (R) Study : Short-term Safety of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema

Objective: To study the safety and tolerability of Lymfactin (R) treatment combined with microvascular lymph node transfer surgery in patients with upper limb lymphedema. Background: Upper limb lymphedema is a common clinical challenge after breast cancer surgery and/or radiotherapy. Lymfactin (R) is an adenovirus type 5-based gene therapy involving expression of human vascular endothelial growth factor C (VEGF-C) in the damaged tissue. It aims to correct deficient lymphatic flow by promoting the growth and repair of lymphatic vessels. Methods: In Phase I, Lymfactin (R) was combined with microvascular lymph node transfer surgery to study the safety and tolerability of Lymfactin (R) and the biodistribution of the viral vector in patients with upper limb lymphedema. Results: Fifteen patients with breast cancer-associated secondary lymphedema of the upper arm were recruited between December 2016 and February 2018. Three patients received a lower dose (1 x 10(10)) and 12 a higher dose (1 x 10(11)) of viral particles, respectively. No dose-limiting toxicities were observed, and the study was completed with the pre-determined maximum dose. Commonly reported adverse events during the 12-month follow-up were common cold, fever, gastroenteritis, pain in the operation area, headache, muscle ache and elevated liver enzymes. Serious adverse events consisted of two erysipelas infections in the lymphedema arm (requiring hospitalization) and one hematoma of the flap donor site. Conclusions: After 12 months' follow-up, results indicate that Lymfactin (R) is well tolerated. The study continues with a 36-months efficacy and 5 years safety follow-up of the patients. The oncological safety aspects of Lymfactin (R) will require a longer follow-up period. (c) 2020 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Pub-lished by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe

Phase 1 LymfactinⓇ Study: Short-term Safety of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema

Objective: To study the safety and tolerability of LymfactinⓇ treatment combined with microvascular lymph node transfer surgery in patients with upper limb lymphedema.Background: Upper limb lymphedema is a common clinical challenge after breast cancer surgery and/or radiotherapy. LymfactinⓇ is an adenovirus type 5–based gene therapy involving expression of human vascular endothelial growth factor C (VEGF-C) in the damaged tissue. It aims to correct deficient lymphatic flow by promoting the growth and repair of lymphatic vessels.Methods: In Phase I, LymfactinⓇ was combined with microvascular lymph node transfer surgery to study the safety and tolerability of LymfactinⓇ and the biodistribution of the viral vector in patients with upper limb lymphedema.Results: Fifteen patients with breast cancer–associated secondary lymphedema of the upper arm were recruited between December 2016 and February 2018. Three patients received a lower dose (1 × 1010) and 12 a higher dose (1 × 1011) of viral particles, respectively. No dose-limiting toxicities were observed, and the study was completed with the pre-determined maximum dose. Commonly reported adverse events during the 12-month follow-up were common cold, fever, gastroenteritis, pain in the operation area, headache, muscle ache and elevated liver enzymes. Serious adverse events consisted of two erysipelas infections in the lymphedema arm (requiring hospitalization) and one hematoma of the flap donor site.Conclusions: After 12 months’ follow-up, results indicate that LymfactinⓇ is well tolerated. The study continues with a 36-months efficacy and 5 years safety follow-up of the patients. The oncological safety aspects of LymfactinⓇ will require a longer follow-up period.</p

Phase 1 Lymfactin® Study: 24-month Efficacy and Safety Results of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema

BACKGROUNDLymphedema is a common problem after breast cancer treatment. Lymfactin® is a prolymphangiogenic growth factor vector inducing the expression of human vascular endothelial growth factor C (VEGF-C). It promotes growth and repair of lymphatic vessels.METHODSLymfactin® was combined with microvascular lymph node transfer surgery (VLNT) to study the safety and efficacy of the treatment in breast cancer-related upper limb lymphedema (BCRL) patients. This is a continuation study with a 3 year efficacy and 5 year safety follow-up.RESULTSFifteen patients were recruited in the study between June 2016 and February 2018. Three patients received a lower dose (1 × 1010 viral particles (vp)), and 12 patients received a higher dose (1 × 1011 vp) of Lymfactin®, respectively. In the higher dose group, the reduction of excess arm volume was on average 46% after the 12 month follow-up, and the transport index was improved in 7/12 patients. At baseline, removal of the compression garment for 7 days resulted in significant arm swelling (105.7±161.0 ml, p=0.0253). However, at 12 months, there was less and not significant swelling after removal of the garment (84.4±143.0 ml, p=0.0682). Lymphedema Quality of Life Inventory (LQOLI or LyQLI) questionnaire showed significant and sustained improvement of quality of life.CONCLUSIONSDuring 24 months' of follow-up, the results indicate that Lymfactin® is well tolerated. The most promising findings were a 46% reduction in excess arm volume and a nonsignificant volume increase after garment removal at 12 months, suggesting that there is potential for the reduction of lymphedema.</p

"Tehdään niinku jotain yhdessä" : lastenkodin omahoitajahetki lapsen näkökulmasta

Tämä opinnäytetyö on laadullinen tutkimus ja sen toimeksiantajana toimii Pelastakaa Lapset ry:n lastenkoti. Tutkimuksen tavoitteena oli tuoda esille lastenkodissa asuvien lasten kokemuksia omahoitajahetkistä ja niiden sisällöstä sekä luoda lapsille mahdollisuus vaikuttaa omahoitajahetkien kehittämiseen. Opinnäytetyön tarkoituksena oli tuottaa tietoa lastenkodin henkilökunnan käyttöön kehittämistyön tueksi, nostaa esiin lapsen ääni ja tukea lapsen edun huomioimista. Tutkimustehtävä oli: Mikä on lapsen kokemus omahoitajahetkistä ja niiden merkityksestä? Opinnäytetyön teoriaosuus koostuu tutkimuksemme kannalta tärkeistä käsitteistä, sosiaalipedagogiikasta, osallisuudesta, dialogisuudesta sekä kiintymyssuhdeteoriasta. Tutkimus tehtiin keväällä 2015 haastattelemalla kuutta lastenkodissa asuvaa lasta, kerätty aineisto analysoitiin aineistolähtöisellä sisällönanalyysilla. Tutkimustuloksista selvisi, että lasten osallisuuden aste omahoitajahetkien suunnittelussa vaihteli. Osalle lapsista oli erityisen tärkeää tulla kuulluksi, ja jokainen lapsi toivoi enemmän perusteluja hetkien sisältöön. Haastatteluissa ilmeni hajontaa kaikilla omahoitajahetkien toteuttamisen osa-alueilla: sisällössä, suunnitelmallisuudessa, järjestämistiheydessä ja teemojen toteuttamisessa. Omahoitajahetkien etuna lapset kertoivat omahoitajan kanssa vietetyn kahdenkeskisen ajan ja mielekkään toiminnan, mutta esille nousi myös toiveita kutsua omahoitajahetkeen mukaan ystävä tai perheenjäsen.This thesis is a qualitative research and its commissioner is a children’s home owned by Save the Children Finland. The aim of this thesis was to reveal children’s experiences of dedicated moments spent with personal caregiver in the children’s home and to create a possibility for children to influence the development of those moments. The purpose of this thesis was to provide information for the personnel of the children’s home to support the development of the work done with children, to raise the children’s own voice and enhance the consideration of the children’s best interest. The research question was: What kind of experience do children have of dedicated moments spent with a personal caregiver and the importance of those moments? The theoretical part of this thesis consist of social pedagogy, participation, dialogue and attachment theory. The research was made during spring 2015 by interviewing six children living in a children’s home. The research material was analyzed with a content analysis method. Based on the research, there is a variety in the degree of childrens' participation in planning the dedicaded moments. For some children it was very important to be heard, but everyone wanted more reasoning about the choices in the content of the dedicaded moments. The interviews also showed variety in content, planning, frequency and execution of chosen themes of those shared moments. The advantages of time spent with a personal caregiver in children’s opinion are the possibility to spend time alone with a personal caregiver and the possibility to do something meaningful. The children also mentioned that they would like the possibility to include a family member or a friend